This invention relates to micromachined devices for receiving and retaining at least one liquid droplet, methods of making the devices and methods of using the devices.
In many applications, from the fabrication of solid-state chemical sensors to preparation of biomedical test plates, it is important to be able to dispense a known quantity of liquid onto a solid surface, and to have it confined to desired lateral dimensions, A good example of this is the deposition of polymeric membrane solutions for potentiometric liquid chemical sensors. The size (and therefore cost) of these sensors is usually determined by the membrane dimensions and spacing.
The size of integrated ion sensors is dictated by the size and spacing of their polymeric membranes, rather than by the size of the associated circuitry. Polymeric membranes have been developed for automated deposition by screen printing, as shown by R. W. Hower et al., xe2x80x9cNew Solvent System for the Improved Electrochemical Performance of Screen-Printed Polyurethane Membrane-Based Solid-State Sensorsxe2x80x9d, PROCEEDINGS FOR TRANSDUCERS 95/EUROSENSORS IX, June 1995, pp. 858-862.
Such automated deposition can also be done with dispensing equipment as shown by S. Anna et al., xe2x80x9cAn IC-Technology Compatible Automatic Method (SCZ Method) for Immobilization Membranesxe2x80x9d, SENSORS AND ACTUATORS, vol. B1, pp. 514-517, 1990.
In both cases, membrane components are dissolved in solvents which are evaporated subsequent to deposition. The area occupied by an array of these membranes can be significantly reduced through the use of wells, areas separated by barrier walls, into which the membrane solutions are deposited. Thick wells for screen-printed membranes are shown by the above-noted article by Hower et al.
Membrane design rules are typically dictated by the requirement of keeping membranes which are selective to different chemicals from touching. If these membranes touch, their ionophores intermix, causing cross-contamination. As mentioned above, membranes can be deposited automatically by either screen-printing or dispensing equipment. The membrane components are dissolved in solvents to form a paste for screen-printing or a liquid for dispensing. Membrane design rules have needed to allow for flow-out of the paste or dispensing solution after it is applied to the sensor surface, making the sensors much larger than they would otherwise need to be.
To reduce the size of screen-printed sensor arrays, wells, as illustrated in FIGS. 1a and 1b, have been formed which limit the flow-out of the membrane components, allowing membranes to be smaller and closer together, as further shown in the above-noted article by Hower et al. These wells provide the additional advantage of making final membrane thickness more uniform and the deposition process more tolerant of variations in the viscosity of membrane solutions.
Epoxies, acrylic photo polymers, thick film polyimide, and silicon have been used to form wells or cavities, as further shown in U.S. Pat. No. 5,200,051 issued to Cozzette et al., and the articles by L. J. Bousse et al., xe2x80x9cSilicon Micromachining in the Fabrication of Biosensors Using Living Cellsxe2x80x9d, TECHNICAL DIGEST, IEEE Solid-State Sensor and Actuator Workshop, Hilton Head, S. C., p. 173-6; June 1990; and R. Eugster et al., xe2x80x9cSelectivity-Modifing Influence of Anionic Sites in Neutral-Carrier-Based Membrane Electrodesxe2x80x9d, ANALYTICAL CHEMISTRY, vol. 63, pp. 2285-2289 (1991).
The approaches previously described are quite acceptable for screen-printed silicone and polyurethane membranes, as they are viscous, thixotropic pastes.
Several epoxies have excellent chemical compatibility with the membranes as well as good membrane adhesion and screen-printing properties, as shown by the article by R. W. Hower et al., xe2x80x9cStudy of Screen-Printed Epoxies for Wells in Solid-State Ion Selective Electrodesxe2x80x9d, TECHNICAL DIGEST, IEEE Solid-State Sensor and Actuor Workshop, Hilton Head Island, S.C., 1996. Membrane solutions optimized for dispensing, on the other hand, have low viscosities and a high solvent-to-solids ratio to keep the dispensing tip from clogging; the composition of a typical membrane is over 90% solvent. When these low-viscosity membrane cocktails are dispensed into the thick wells, the membranes wick out of the wells through surface tension, thinning the resulting membranes and enlarging the required membrane area.
Microsensors are sensors that are manufactured using integrated circuit fabrication technologies and/or micromachining. Integrated circuits are fabricated using a series of process steps which are done in batch fashion, meaning that thousands of circuits are processed together at the same time in the same way. The patterns which define the components of the circuit are photolithographically transferred from a template to a semiconducting substrate using a photosensitive organic coating. The coating pattern is then transferred into the substrate or into a solid-state thin-film coating through an etching or deposition process. Each template, called a xe2x80x9cmaskxe2x80x9d, can contain thousands of identical sets of patterns, with each set representing a circuit. This xe2x80x9cbatchxe2x80x9d method of manufacturing is what makes integrated circuits so reproducible and inexpensive. In addition, photoreduction enables one to make extremely small features. The resulting integrated circuit is contained in only the top xc2xc micron or so of the semiconductor substrate and the submicron thin films on its surface. Hence, integrated circuit technology is said to consist of a set of planar, microfabrication processes.
Micromachining refers to the set of processes which produce three-dimensional microstructures using the same photolithographic techniques and batch processing as for integrated circuits. Here, the third dimension refers to the height above the substrate of the deposited layer or the depth into the substrate of an etched structure. Micromachining produces third dimension in the range of 1-500 xcexcm (typically). The use of microfabrication to manufacture sensors produces the same benefits as it does for circuits: low cost per sensor, small size, and highly reproducible behavior. It also enables the integration of signal conditioning, compensation circuits and actuators, i.e., entire sensing and control systems, which can dramatically improve sensor performance for very little increase in cost. For these reasons, there is a great deal of research and development activity in microsensors.
An object of the present invention is to provide a micromachined device for receiving and retaining at least one liquid droplet, method of making the device and method of using the device wherein the at least one droplet is retained on the device through surface tension.
In carrying out the above object and other objects of the present invention, a micromachined device for receiving and retaining a liquid droplet at a desired site is provided. The device includes a substrate having an upper surface, and a three-dimensional, thin film well patterned at the upper surface of the substrate. The well is capable of receiving and retaining a known quantity of liquid at the desired site through surface tension.
In further carrying out the above object and other objects of the present invention, a micromachined device for receiving and retaining at least one liquid droplet at a desired site is provided. The device includes a substrate having an upper surface, and a first three-dimensional, thin film well patterned at the upper surface of the substrate. The first well is capable of receiving and retaining a first known quantity of liquid at the desired site through surface tension. The devices also includes a second three-dimensional, thin film well patterned at the upper surface of the substrate. The second well is patterned outside and concentric to the first well and is capable of receiving and retaining a second known quantity of liquid at the desired site through surface tension.
In further carrying out the above object and other objects of the present invention, a micromachined device for receiving and retaining a plurality of separate liquid droplets at desired sites is provided. The device includes a substrate having an upper surface, and an array of three-dimensional, thin film wells patterned at the upper surface of the substrate. Each of the wells is capable of receiving and retaining a known quantity of liquid at one of the desired sites through surface tension.
In further carrying out the above object and other objects of the present invention, a micromachined device for receiving and retaining a plurality of separate liquid droplets at desired sites is provided. The device includes a substrate having an upper surface, and a first array of three-dimensional, thin film wells patterned at the upper surface of the substrate. Each of the wells is capable of receiving and retaining a known quantity of liquid at one of the desired sites through surface tension. The device also includes a second array of three-dimensional, thin film wells patterned at the upper surface of the substrate. Each well of the second array of wells is patterned outside and concentric to one well of the first array of wells to receive and retain a second known quantity of liquid at the desired site through surface tension.
Each of the wells may be a ring.
The device may be a microsensor wherein each of the desired sites is a sensing site. The microsensor may be a solid-state, liquid chemical sensor.
The microsensor may be a gas sensor or an optical sensor.
The device may be a biomedical test plate.
Each of the wells may be made of a photo-patternable material wherein the material may be a negative photo-patternable material.
The negative photo-patternable material may be a polymer wherein the polymer may be a polyimide.
The negative photo-patternable material may also be an epoxy wherein the epoxy may be SU8.
The substrate may be a semiconductor substrate and may include a silicon wafer.
The semiconductor substrate may further include a layer of insulating material on which the wells are patterned.
The substrate may be made of a material other than a semiconductor material.
The device may be a potentiometric liquid chemical sensor wherein each desired site is a sensing site.
The device may also be an integrated ion sensor wherein each desired site is a sensing site.
Each of the wells may include a side wall having an outside corner with a small radius to prevent its liquid droplet from flowing down outside the side wall.
In further carrying out the above object and other objects of the present invention, a method of making a micromachined device which is capable of receiving and retaining at least one liquid droplet is provided. The method includes providing a substrate having a layer of radiation-sensitive material formed thereon. The method also includes patterning at least one three-dimensional, thin film well from the layer of material. The at least one well is capable of receiving and retaining a known quantity of liquid through surface tension.
The method may further include patterning a three-dimensional, thin film well from the layer of material outside and concentric to the at least one well at the same time as patterning the at least one well.
The layer of material may be photo-patternable.
A method of using a device which has one well is further provided. The method includes dispensing a membrane solution droplet into the well wherein the membrane solution may be a polymeric membrane solution, an aqueous solution, or a solvent-based solution.
The membrane may be an optical membrane.
A method of using a device which as a second well outside and concentric with a first well includes dispensing a first membrane solution droplet into the first well, and dispensing a second membrane solution droplet over the first membrane solution droplet and into the second well.
The first membrane solution may be an internal filling solution.
The second membrane solution may be an external binding layer.
The second membrane solution may have enzymes, antibodies or fictional groups trapped therein.
A method of using a device which has a first array of wells is further provided. The method includes dispensing a membrane solution droplet into each of the wells of the array.
A method of using a device which has first and second arrays of wells wherein each of the second array of wells is outside and concentric with a well of the first array includes dispensing a first membrane solution droplet into each of the first array of wells, and dispensing a second membrane solution droplet over each of the first membrane solution droplets and into each of the second array of wells.
The substrate may be a semiconductor substrate such as a silicon wafer. The semiconductor substrate may further include a layer of insulating material on which the wells are patterned. The insulating material may include silicon nitride, silicon dioxide, silicon carbide, diamond, Teflon, etc.
The substrate may be made of glass, ceramic, plastic, metal, or other material.
Each of the wells preferably has a side wall with a rounded outside corner. An outside edge of each of the wells may have a negative profile or, alternatively, have other profiles such as vertical or positive profiles. In all cases, it is preferable to have a small radius at the outside corner.
The technique works for both aqueous and solvent-based solutions.
These wells can be utilized for containing any solution either aqueous or a solvent-based polymer film in a reproducible fashion, with reduced size and decreased spacing.
Polymer wells of the invention can be used to contain a polymer film used as a preconcentrator for a micromachined gas chromatograph system. These membranes can be cast in much the same way as the liquid chemical sensors, providing a small reproducible surface area and volume membranes to be used in this device.
The invention can also be used to pattern membranes for optically coupled sensors, in which the opacity of the membrane changes with chemical concentration.
The wells can be used to contain multilevel membranes, such as those using an internal filling solution, and an external binding layer.
A second set or array of well rings, photo-patterned at the same time as the first set or array, can be used to isolate functional groups on top of ion-selective membranes. The improved functionality can be accomplished by entrapping enzymes, antibodies, or functional groups, which can be later used to photo immobilize enzymes or antibodies, on the surface. A second membrane is dispensed on top of the first membrane with the functional groups entrapped in this external membrane. The external membrane will completely cover the first, and will flow out to the outer rings. This asymmetric membrane allows the liquid chemical sensors to monitor chemicals other than ions and in much lower concentrations, by catalyzing a reaction and detecting a byproduct. Using this asymmetric membrane technique, it is often very important to reproducibly immobilize known quantities of enzyme or antibody on the surface to get a reproducible signal. Often these devices are one-shot sensors and cannot be calibrated. Using these wells allows the mass production of reproducible enzyme or antibody layers on the surface of the ISE (ion selective electrode).
The device, method for making the device, and the method for using the device of the present invention are general. While particular implementations of the invention are disclosed herein, it would work with other materials having similar surface properties as well. There are many potential uses for this invention even though the invention was specifically developed for solid-state liquid chemical sensors.
The above object and other objects, features, and advantages of the present invention are readily apparent from the following detailed description of the best mode for carrying out the invention when taken in connection with the accompanying drawings.